This S10 application requests funds for a Bruker X8 Prospector integrated diffraction system along with an Oxford cryostream to replace the aging system within the Department of Biochemistry and Molecular Biology at the Indiana University School of Medicine. The user group consists of 6 major users, 4 of whom are NIH funded investigators with 10 active grants and an additional 5 pending NIH grants. In addition, two new outstanding new faculty members with national-level funding from AHA and NSF, as well as the Michael J. Fox Foundation are part of the user group. X-ray crystallography is a powerful tool for the study of macromolecular structure. The research supported by this instrumentation request will lead to a better understanding of the roles our target proteins play in health and disease. Many of our major users are also involved in drug discovery research, which may ultimately lead to improved therapeutic approaches to treat diseases such as alcoholism, cardiovascular disease, diabetes, neurodegenerative disorders and cancer. The new instrumentation will be integrated into our existing X- ray crystallography facility by replacing the over 16 year-old H2R rotating anode generator. The upgrade of our facilities will allow our productive research faculty to remain competitive in the NIH funding environment and will undoubtedly lead to new advances in our understanding of the function of biomedically relevant macromolecules. PUBLIC HEALTH RELEVANCE: X-ray crystallography is a powerful tool for the study of macromolecular structure. The research supported by this instrumentation request will lead to a better understanding of the roles our target proteins play in health and disease. Many of our major users are also involved in drug discovery research which may ultimately lead to improved therapeutic approaches for diseases such as alcoholism, cardiovascular disease, diabetes and cancer.